Search PubMed⌕ Search

Biomedical subjects

Y Tsukada

Publications and source records attributed to Y Tsukada.

At least 163 records · Page 9Linked to original sources

Patterns of metastasis in uterine sarcoma. An autopsy study.

The autopsy findings of 73 patients with uterine sarcoma were studied to determine the sites and possible modes of metastasis. Homologous mixed mesodermal tumors were the most frequent (41%) followed by leiomyosarcoma (26%), heterologous mixed mesodermal tumor (18.3%), stromal sarcoma (12%), and endolymphatic stromal myosis (3%). The peritoneal cavity and omentum were the most frequently involved sites (59%), followed by the lung (52%), pelvic lymph nodes (41%), paraaortic lymph nodes (38%), and liver parenchyma (34%). The presence of lung metastasis was not associated with pelvic or paraaortic node metastasis or intraperitoneal disease. Metastasis to other distant sites including the brain, heart, kidney, and bone were independent of pelvic and paraaortic nodal metastasis or intraperitoneal disease. Metastatic sites were not different among various histologic types. Distant metastatic sites were statistically associated with lung metastasis. Hematogenous metastasis best explains this metastatic pattern and adjuvant systemic therapy seems indicated.

Adult↗

Co-culture of fibroblasts and hepatic parenchymal cells induces metabolic changes and formation of a three-dimensional structure.

Co-culturing of tendon fibroblasts and liver parenchymal cells in Williams' medium E supplemented with fetal bovine serum, hormones, and L-ascorbic acid 2-phosphate, a long acting vitamin C derivative, resulted in formation of three-dimensional structure. Both growth of fibroblasts and their production of collagen were inhibited, however production of albumin by the hepatocytes was much better preserved than when individual cells were cultured separately, indicating epithelial-mesenchymal interactions stimulate reorganization of the liver-like tissue from isolated cells.

Achilles Tendon↗

Serum levels and biochemical characteristics of human ovarian carcinoma-associated antigen defined by murine monoclonal antibody, CF511.

The murine monoclonal antibody (Mab) against human common epithelial ovarian carcinoma, CF511, was generated by immunising mice with human fetal tissue extract from early first trimester, followed by booster injection of an ovarian cancer cell line. Mab CF511 recognised the 600 kDa sialylated glycoprotein as different from previously known tumour associated-marker antigens. Distribution of the Mab CF511-recognised antigen (CF511 antigen) in various tissues and sera was investigated. In immunohistochemical analysis, Mab CF511 reacted strongly with tumour cells of ovarian serous, clear cell, endometrioid and undifferentiated carcinoma and partially with those of mucinous carcinoma. Mab CF511 also reacted with breast carcinoma as well as lung carcinoma. In normal tissues, Mab CF511 cross-reacted with only five tissues, namely lung, breast, thyroid gland, fallopian tube and uterus. Serum levels of CF511 antigen were tested by ELISA inhibition using Mab CF511. This assay showed the circulating CF511 antigen levels to be elevated in 25 of 36 sera from patients with various clinical stages of common epithelial ovarian carcinoma compared to three of 47 and three of 111 sera from patients with other benign gynaecological diseases, including ovarian cysts, uterine fibroids with or without endometriosis and normal healthy subjects, respectively. For the relation between antigen levels and clinical stages of common epithelial ovarian carcinoma, greater than 34.0% ELISA inhibition was detected in 100% of patients with advanced stages (FIGO III and IV) compared with in 35.3% with early stages (FIGO I and II) patients. While patients with breast carcinoma (100%) and lung carcinoma (100%) also had elevated circulating CF511 antigen levels, patients with hepatoma, colorectal carcinoma and gastric carcinoma had no detectable elevation of antigen. Although the test showed a high degree of specificity, the detection of an elevated CF511 antigen level would not be so helpful in distinguishing patients with ovarian carcinoma from those with either breast carcinoma or lung carcinoma. These data suggest that CF511 antigen is a useful new ovarian tumour marker for diagnosis and management of the disease.

Adult↗

Purification and properties of neuraminidase isozymes in Arthrobacter ureafaciens mutant.

An Arthrobacter ureafaciens mutant (M1057) capable of producing neuraminidase constitutively was isolated by NTG mutagenesis from A. ureafaciens KMS 3663. Four molecular species (L, M1, M2, and S) of neuraminidase isozymes were homogeneously purified from the mutant and parent strains by means of DEAE-cellulose, affinity chromatography, ammonium sulfate precipitation, chromatofocusing, and Ultrogel AcA44 gel filtration. The molecular weights of L, M1, M2, and S isozymes were shown to be approximately 88,000, 66,000, 66,000, and 52,000, respectively. The optimal pHs and Km values of these isozymes for N-acetylneuraminosyl-alpha,(2-6)-lactose were 4.5-5.5 and 0.6-0.8 mM. Neuraminidase L, M1, M2, and S were able to hydrolyze oligosaccharides, glycoproteins and gangliosides containing alpha,(2-3)-, alpha,(2-6)-, and alpha,(2-8)-linked N-acetylneuraminic acid. Among these isozymes isolated, isozyme S was most active on colominic acid.

Arthrobacter↗

Synthesis of L-3,4-dihydroxyphenylalanine by tyrosine hydroxylase cDNA-transfected C6 cells: application for intracerebral grafting.

In the present study, we obtained genetically manipulated nonneuronal cells which synthesize a catecholamine precursor for future use in intracerebral grafting. Human type 1 tyrosine hydroxylase (TH; EC 1.14.16.2) cDNA was inserted into eukaryotic expression vector pKCRH2 and was co-transfected into C6 cells with plasmid pSV2neo. Expression of the TH minigene was screened by immunohistochemical staining with TH antibody and immunoblotting analysis. Several clones of the C6 transfectants that produce TH molecules were obtained. These cells showed TH activity, and the product, L-3,4-dihydroxyphenylalanine (L-DOPA), was detected intracellularly due to the absence of L-amino acid decarboxylase (EC 4.1.1.28) activity. It was found that a large amount of L-DOPA was released from the cells into the culture medium. These transfectants were transplanted into rat brain, and the expression of TH was examined immunohistochemically. On the 10th day following transplantation, a mass of C6 cells which was heavily stained with TH antibody was observed in the brain. These findings may provide us with an opportunity to investigate the effects of intracerebral transplantation of nonneuronal cells that produce catecholamine or its precursor.

Animals↗

An improved sensitive assay method for the heterogeneity of alpha-foetoprotein: possible application for early differential diagnosis.

A combination of lectin-affinity electrophoresis and antibody-affinity blotting was used for the qualitative determination of molecular species of alpha-foetoprotein. Concanavalin A and erythrophytohaemagglutinin were used as lectins. This method was able to quickly discriminate between the molecular species of alpha-foetoprotein of recurrent ovarian yolk sac tumour and those of non-malignant liver diseases and cord sera at term, using only 3 microliters of sera containing 200 micrograms/l of alpha-foetoprotein. The results indicate that this assay method might be useful for the differential diagnosis of recurrent yolk sac tumour from drug- or blood transfusion-induced liver diseases and for the monitoring of the serum alpha-foetoprotein level of patients with yolk sac tumour producing less than 200 micrograms/l of alpha-foetoprotein.

Antibodies↗

[The effect of hypotensive anesthesia with nitroglycerin and verapamil on platelets].

Recently, there have been many cases in which nitroglycerin (TNG) is used for anesthesia for patients with low blood pressure. Since, it has been reported that TNG suppresses the platelet aggregation function in vitro. Verapamil (Vp), known as another platelet aggregation suppressant, and nicardipine (Nc) were used together with TNG and the platelet aggregation function was studied in vitro and in vivo. The results of the in vitro experiment showed that TNG 250 ng.ml-1 + Vp 250 ng.ml-1 suppressed the platelet aggregation function, and when TNG + Vp (was used for low hypotensive anesthesia, a large amount of Vp i.e. over 15 mg of Vp is injected as a bolus into the artery, there is a possibility the platelet aggregation function will be suppressed. No platelet aggregation function suppression was found when TNG+Nc was used in hypotensive anesthesia.

Drug Combinations↗

Immunological response and oesophageal varices in PBC.

A retrospective study was made of the clinical features, especially oesophageal varices, of 93 patients with PBC. The 5 year survival rate of asymptomatic PBC patients was 88.7% and that of symptomatic PBC was 43.7%. The 5 year survival rate of the group with oesophageal varices was 44.0% and that of the group without varices was 68.8%. The 5 year survival rate of the patients with high-risk varices was 39.1% and of those without high-risk varices was 67.9%. Management of variceal bleeding in PBC patients was considered very difficult. In prognostic study, the patients with the prophylactic therapy were better than the patients with emergency or elective therapy. The antiM8 (a subtype of antimitochondrial antibody) positive patients had poor prognosis compared with antiM8 negative patients. Therefore, it was concluded from these data that some kind of treatment was necessary for patients with high-risk varices. In particular, it was considered necessary to monitor closely the patients whose serum alkaline phosphatase levels had remained high.

Adult↗

Pathologic complete response of advanced ovarian mixed mesodermal tumor to cisplatin, adriamycin and dacarbazine: a case report.

Presented is a case report of a stage IIIC primary ovarian mixed mesodermal tumor with gross residual disease following aggressive cytoreductive surgery. Following twelve courses of Cisplatin, Adriamycin and Dacarbazine, second-look laparotomy confirmed a pathologic complete response. The patient is now free of disease at 17+ months.

Antineoplastic Combined Chemotherapy Protocols↗

Detection of a novel antigen (1G12) on the surface of peripheral blood mononuclear cells from cancer patients by a sensitive radioimmunoassay. A possible marker for the early diagnosis of cancer.

A murine monoclonal antibody designated 1G12 has been produced by immunizing mice with A549 human lung adenocarcinoma. Using radiolabeled monoclonal antibody 1G12, a sensitive radioimmunoassay to detect 1G12 antigen has been developed. The antigen was detected on the surface of peripheral blood mononuclear cells (PBMC). A study was performed to examine the frequency of distribution of this antigen on the surface of PBMC from healthy donors and patients with cancer. An antigen level of above 30 units per 1 x 10(6) PBMC was considered positive. None of 41 healthy donors (0%) and 16 of 96 patients (16.7%) with benign diseases of the lung, ovary, and uterus were positive. In contrast, 27 of 41 patients (65.8%) with lung cancer, 14 of 18 patients (77.8%) with ovarian cancer, and 16 of 27 patients (59.2%) with uterine cervical cancer had elevated levels of 1G12 antigen. When patients were grouped by stages of cancer, PBMC from patients in relatively early stages (stages I and II) also gave positive results, i.e., 9 of 17 patients (59.2%) with lung cancer, 6 of 10 patients (60%) with ovarian cancer, and 11 of 22 patients (50%) with uterine cervical cancer of these stages were positive. These results suggest that the detection of 1G12 antigen on PBMC of patients may be useful for early diagnosis of cancers.

Adolescent↗

The effect of bispecific monoclonal antibody recognizing both hepatoma-specific membrane glycoprotein and anthracycline drugs on the metastatic growth of hepatoma AH66.

A monoclonal mouse antibody (MoHG) was produced using in vitro cultured AH66R tumor cells treated with cholesteryl hemisuccinate as an immunogen. The antibody identified a 90 kd membrane glycoprotein (HG-90) which is expressed on in vitro cultured hepatoma cell lines AH66 and AH66R. A monoclonal antibody was prepared to the anthracycline drug daunomycin, and it also reacted with adriamycin. A fusion was made of the hybridoma HG-90 with the hybridoma which recognized daunomycin/adriamycin. This bispecific hybridoma A8C recognized both determinants. We studied the therapeutic effect of the A8C bispecific antibody with adriamycin treatment and compared it to the effect of the bispecific antibody to which adriamycin had been conjugated via an albumin (Alb) bridge. The therapy model used was the tumor AH66R in Donryu rats. Tumor bearing rats had their subcutaneous tumors resected on day 10, a time when distant metastases were present. After the surgical resection of the tumor the rats were injected intravenously for two cycles with the bispecific antibodies, followed by the administration of adriamycin (ADR) or MoHG.Alb.ADR conjugates. A slight therapeutic effect occurred with either MoHG or ADR alone but treatment with the bispecific antibody followed by the administration of ADR or with the MoHG.Alb.ADR conjugates significantly prolonged survival, with 60% of the treated animals being "tumor free" when sacrificed on day 80. Lower serum concentrations of alphafetoprotein were observed with the bispecific antibody and drug treatment. This suggests that the bispecific antibody/drug treatment is potentially more beneficial in the suppression of distant metastases than the MoHG.Alb.ADR conjugate. This may be due to an increase in the local drug concentration of unmodified adriamycin.

Animals↗

Immunohistochemical studies on the proliferation of reactive astrocytes and the expression of cytoskeletal proteins following brain injury in rats.

The appearance of reactive astrocytes following brain injury was investigated in 4-week-old rats with special reference to their proliferation and chronological changes in the cytoskeletal proteins. Two days after the injury, glial fibrillary acidic protein (GFAP)-positive cells had increased in number around the lesion and spread to the entire ipsilateral cortex by 3 days after the injury. To investigate the distribution of mitotic cells and its chronological change, immunohistochemical staining with monoclonal antibody to bromodeoxyuridine (BrdU) was performed. BrdU-positive cells began to appear around the lesion and spread to the entire ipsilateral cortex by 3 days and their distribution was the same as that of GFAP-positive cells. To investigate the association of GFAP-positive cells with cell division, double labeling experiments using [3H]thymidine autoradiography and immunohistochemical staining with antiserum to GFAP were performed. Cells doubly labeled with GFAP and [3H]thymidine were localized in the area adjacent to the lesion, in the molecular layer of the cortex and in the white matter. By contrast, none of the cells were doubly labeled in the IInd to VIth layers of the cortex. Furthermore, only astrocytes in the former areas expressed vimentin transiently from 2 to 10 days after the injury. In the rats administered vincristine, cells arrested during mitosis were found in the regions which express vimentin. From these results, it was suggested that astrocytes in the molecular layer of the cortex and the white matter adjacent to the lesion proliferated in response to the injury and expressed vimentin transiently, then acquired GFAP, and that astrocytes in the IInd to VIth layers of the cortex became reactive astrocytes without mitosis.

Animals↗

Stage I uterine adenosarcoma: a report of six cases.

Six cases of Stage I adenosarcoma of the uterus are reported. Although these neoplasms have generally been regarded as being of low malignant potential with little propensity for distant metastasis, our experience reveals some of them to be aggressive tumors with rapid clinical demise. Five (83%) patients demonstrated recurrence after initial surgery, three despite postoperative vaginal radium or external pelvic radiation. Four of the recurrences occurred in the pelvis and abdomen; the fifth was limited to the vagina. Three patients were dead of disease within three years of diagnosis, two of whom achieved clinical remission for at least one year to combination chemotherapy. One of the remaining three patients died from intercurrent disease without recurrence, and two are alive without disease after treatment for recurrence. Based on this limited experience, we believe these neoplasms should be regarded as potentially as malignant as their mixed Müllerian counterpart.

Antineoplastic Combined Chemotherapy Protocols↗

Possible synapse formation by embryonic cerebellar tissue grafted into the cerebellum of the weaver mutant mouse.

The weaver mutant mouse is characterized by degeneration of cerebellar granule cells in early post-natal stage. In the present study, the possibility of synapse formation in the weaver mouse cerebellum by implanted granule cells was analyzed immunohistochemically with antiserum against synaptic vesicle protein, Synapsin I. Normal cerebellar tissue, obtained from 15-day-old CBA/JNCij mouse embryos, was transplanted into the cerebellum of 4-week-old weaver mice. 6 weeks after the transplantation, the grafted tissue was clearly detected in the host cerebellum, developing a trilaminar organization. A number of granule-like cells were observed in the folia of the host cerebellum, suggesting that the implanted granule cells may have migrated from the grafted tissue into the host cerebellum. Some areas in the host cerebellum as well as in the grafted tissue were intensely stained by anti-Synapsin I serum, indicating that the implanted granule cells make synaptic contacts with the neuronal cells.

Animals↗

Restoration of microcephalic cerebrum with hypomyelination in the growth hormone-deficient mouse (lit): stimulatory effects of GH restricted to the first 20 days of postnatal life.

We administered bovine growth hormone to the Little (lit), a promising model of isolated growth hormone deficiency, during the first and second 20 days after birth. Positive results were obtained only when bovine growth hormone was given during the first 20 days of postnatal life. We observed a distinct increase in cerebral weight, DNA content, and 2',3'-cyclic nucleotide 3'-phosphohydrolase activity. The latter administration of bovine growth hormone was ineffective. These data prove that growth hormone has an independent action on cerebral development, apart from the complementary or synergistic action of thyroid hormones, and that the administration of exogenous growth hormone led to increased myelinogenesis through its stimulatory effects on glial proliferation, as evidenced by the increase in cerebral DNA content.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Conservative therapy for melanoma of the vulva.

Recent cooperative studies have demonstrated that less radical local resection of cutaneous melanomas is equally effective as a traditional radical approach. A retrospective review of vulvar melanoma was undertaken to determine if mode of therapy affected recurrence. Survival correlated independently with depth of invasion and age (p = 0.05 and p less than 0.02, respectively). In the comparison of radical vulvectomy with local excision, no patient differences in age or histopathologic variables were determined (nodal disease status, histology, mitotic count, lymphocytic infiltration, or ulceration). Radical vulvectomy did not improve survival over local therapy (p greater than 0.2). Six of eight patients whose melanoma had less than 2 mm of invasion treated with local therapy are disease free after a median of 127 months (range 6 to 300 months). For local excision, recurrences were more frequent when margins were less than 2 cm, but this was not statistically significant in this small sample. Although the current series is small and retrospective, its findings suggest that treatment recommendations of large cutaneous nonvulvar melanoma studies are applicable to vulvar melanoma. A prospective randomized study of radical versus conservative surgery for vulvar melanoma will be necessary to confirm these treatment recommendations.

Adult↗

Reorganization of cerebellar cell suspension transplanted into the weaver mutant cerebellum and immunohistochemical detection of synaptic formation.

Dissociated cells prepared from the cerebellar primordia of normal 15-day mouse embryos were grafted into the cerebellum of 1-month-old weaver mutant mice which are characterized by degeneration of cerebellar granule cells during the early postnatal period. The growth of the grafted cells was investigated at 1 month after the operation. Implanted cells were highly developed to form a large mass of tissue in the host cerebellar folia. Histological examination revealed that a trilaminar cortical structure was partially developed in certain areas of the grafted tissue. The implanted granule-like cells were labeled with [3H]thymidine which was injected into the host, suggesting that the granule-like cells actively proliferate in the host cerebellum after the transplantation. In this area, strong immunoreactivity with synapsin I was detected indicating that the dissociated granule cells of the cerebellar primordia are able to develop a synaptic organization in the weaver mouse cerebellum.

Animals↗

Peritoneal papillary carcinoma.

Between 1977 and 1986, 325 patients with a diagnosis of ovarian carcinoma, peritoneal cancer, or malignant mesothelioma were reviewed with identification of 23 patients (7%) having peritoneal papillary cancer. Only 2 patients had disease confined to the pelvis and the rest had widespread abdominal disease. Various combination chemotherapeutic agents were used with over a 65% response rate to first-line chemotherapy. Twenty of the 23 patients received cisplatin combination chemotherapy with an overall response rate of 65%.

Adolescent↗